DNA cleavage induced by antitumor antibiotic leinamycin and its biological consequences.
DNA cleavage induced by antitumor antibiotic leinamycin and its biological consequences.
复制标题
抗肿瘤抗生素来那霉素诱导的 DNA 裂解及其生物学后果。
DOI：
10.1016/j.bmc.2012.05.033
复制
发表时间：
2012
影响因子：
3.5
通讯作者：
Sun,Daekyu
中科院分区：
文献类型：
--
作者：
Viswesh,Velliyur;Hays,AllisonM;Gates,Kent;Sun,Daekyu
已发现天然产物雷那霉素通过水解被该药物修饰的鸟嘌呤残基的糖苷键在双链体DNA中产生脱碱基位点。在本研究中，使用合成的寡核苷酸双链体，我们证明了自发的DNA链切割在莱那霉素诱导的脱碱基位点通过β-消除反应。然而，甲氧胺修饰来那霉素诱导的脱碱基位点被发现对自发的β-消除反应是难治的。此外，该配合物甚至抵抗热哌啶处理的δ-消除反应。博莱霉素和甲磺酸甲酯也诱导链切割的合成寡核苷酸双链体，即使没有热处理。然而，甲氧胺对这两种药物诱导的DNA链切割的影响可以忽略不计，这表明雷那霉素诱导的DNA切割机制可能不同于博莱霉素或甲磺酸甲酯诱导的DNA切割机制。在这项研究中，我们还评估了莱那霉素对各种修复途径缺陷的哺乳动物细胞系的细胞毒性。与亲本细胞系相比，核苷酸切除修复（NER）或碱基切除修复（BER）途径缺陷的哺乳动物细胞系对莱那霉素的敏感性约为3至5倍。相比之下，V（D）J重组缺陷的放射敏感性突变xrs-5细胞系显示出与亲本细胞系相似的对雷那霉素的敏感性。总的来说，我们的研究结果表明，NER和BER途径都发挥了重要作用，在修复DNA损伤所造成的莱那霉素。
The natural product leinamycin has been found to produce abasic sites in duplex DNA through the hydrolysis of the glycosidic bond of guanine residues modified by this drug. In the present study, using a synthetic oligonucleotide duplex, we demonstrate spontaneous DNA strand cleavage at leinamycin-induced abasic sites through a β-elimination reaction. However, methoxyamine modification of leinamycin-induced abasic sites was found to be refractory to the spontaneous β-elimination reaction. Furthermore, this complex was even resistant to the δ-elimination reaction with hot piperidine treatment. Bleomycin and methyl methanesulfonate also induced strand cleavage in a synthetic oligonucleotide duplex even without thermal treatment. However, methoxyamine has a negligible effect on DNA strand cleavage induced by both drugs, suggesting that the mechanism of DNA cleavage induced by leinamycin might be different from those induced by bleomycin or methyl methanesulfonate. In this study, we also assessed the cytotoxicity of leinamycin against a collection of mammalian cell lines defective in various repair pathways. The mammalian cell line defective in the nucleotide excision repair (NER) or base excision repair (BER) pathways was about 3 to 5 times more sensitive to leinamycin as compared to the parental cell line. In contrast, the radiosensitive mutant xrs-5 cell line deficient in V(D)J recombination showed similar sensitivity towards leinamycin compared to the parental cell line. Collectively, our findings suggest that both NER and BER pathways play an important role in the repair of DNA damage caused by leinamycin.
登录
查看更多内容
从人类细胞中受损的 DNA 中酶促释放 5-末端脱氧核糖磷酸残基。
影响因子：
2.9
作者：
A. Price;T. Lindahl
通讯作者：
T. Lindahl
药物引起的 DNA 损伤的化学
影响因子：
3.5
作者：
Saito Isao
通讯作者：
Saito Isao
氰化物和膦可以引发莱纳霉素的 DNA 烷基化作用。
影响因子：
2.7
作者：
Zang,H;Breydo,L;Mitra,K;Dannaldson,J;Gates,KS
通讯作者：
Gates,KS
中国仓鼠卵巢X射线敏感突变细胞xrs 5和xrs 6的生化和细胞遗传学特征。五、DNA链断裂和碱基损伤与X射线辐射诱导的染色体畸变和姐妹染色单体交换的相关性。
DOI：
10.1016/0921-8777(90)90065-d
发表时间：
1990
期刊：
Mutation research
影响因子：
--
作者：
F. Darroudi;A. Natarajan;G. P. van der Schans;A. A. van Loon
通讯作者：
A. A. van Loon
影响因子：
4.1
作者：
BAILLY, V;VERLY, WG
通讯作者：
VERLY, WG